Positron emission tomography (PET) allows measurement of receptors in vivo in the human brain. This method has shown enormous promise for gaining insight into the basis of affective disorders, which have long been thought to be associated with the opiate system. The earliest evidence that the opiate system may play a role in the origins of affective disorders appeared in ancient times, when opium was first used to treat depression. Over the centuries, this hypothesis gained additional support, albeit mostly indirect. More recently, autopsy studies, animal models and peripheral measures in humans have provided additional evidence for a link between depression and the opiate system. For the first time, PET provides the opportunity to measure mu-opiate receptors in living subjects with affective disorders. Preliminary results are promising: mu- opiate receptors in the inferior frontal and superior temporal cortex of severely depressed patients are significant increased, further supporting the relationship between opiate receptors and the symptoms of depression. Thus, the overall goal of this proposal is to elucidate the role of mu opiate receptors in affective disorders. The aims are: 1) To measure regional brain mu opiate receptors in unipolar depressed patients using 11/C-carfentanil and PET. HYPOTHESIS: Unipolar affective disorder is associated with increased mu opiate receptors in limbic-related brain regions such as orbital frontal cortex, anterior temporal cortex and cingulate cortex. 2) To determine the relationship of increased mu opiate receptors to quantitative clinical measurements of unipolar affective disorder. HYPOTHESES: i) The severity of depressive symptomatology correlates quantitatively with elevations in regional mu opiate receptors. ii) Improvement in clinical condition following effective drug treatment in unipolar patients correlates with a normalization of regional mu opiate receptors.